Estimation of the relative severity of floods in small ungauged catchments for preliminary observations on flash flood preparedness: a case study in Korea.
An increase in the occurrence of sudden local flooding of great volume and short duration has caused significant danger and loss of life and property in Korea as well as many other parts of the World. Since such floods usually accompanied by rapid runoff and debris flow rise quite quickly with little or no advance warning to prevent flood damage, this study presents a new flash flood indexing methodology to promptly provide preliminary observations regarding emergency preparedness and response to flash flood disasters in small ungauged catchments. Flood runoff hydrographs are generated from a rainfall-runoff model for the annual maximum rainfall series of long-term observed data in the two selected small ungauged catchments. The relative flood severity factors quantifying characteristics of flood runoff hydrographs are standardized by the highest recorded maximum value, and then averaged to obtain the flash flood index only for flash flood events in each study catchment. It is expected that the regression equations between the proposed flash flood index and rainfall characteristics can provide the basis database of the preliminary information for forecasting the local flood severity in order to facilitate flash flood preparedness in small ungauged catchments.


Stretch speed-dependent myofiber damage and functional deficits in rat skeletal muscle induced by lengthening contraction.
Exercise involving lengthening contraction (LC) often results in delayed myofiber damage and functional deficits over the ensuing days. The present study examined whether the stretch speed of LC is a determinant of damage severity. Under isoflurane anesthesia, LC was repeatedly induced in rat ankle extensor muscles at different stretch speeds (angular velocities of 50, 100, 200, and 400 deg/sec) over a fixed stretch range of motion (90°). The number of muscle fibers labeled with Evans blue dye, a marker of muscle fiber damage associated with increased membrane permeability, increased with the angular velocity of LC (by 20% of all myofibers at 400 deg/sec). Muscle fibers with cross-sectional areas in the range of 3600-4800 μm(2), corresponding to type IIb fiber size, exhibited the most severe damage as revealed by the largest decrease in the number of fibers 3 days after LC at 200 deg/sec, suggesting that muscle damage occurred preferentially in type IIb myofibers. Isometric torque of dorsiflexion measured 2 days after LC decreased progressively with LC angular velocity (by 68% reduction at 400 deg/sec). The angular velocity of muscle stretch during LC is thus a critical determinant of the degree of damage, and LC appears to damage type IIb fibers preferentially, resulting in a disproportionate reduction in isometric torque. This LC response is an important consideration for the design of physical conditioning and rehabilitation regimens.


Tracing Dietary Mercury Histochemically, with Autometallography, through the Liver to the Ovaries and Spawned Eggs of the Spot, a Temperate Coastal Marine Fish.
Exposure to mercury (Hg) results in reproductive abnormalities and deficiencies in female fish. We traced the maternal assimilation and redistribution of dietary inorganic (HgII) and organic (MeHg) forms of Hg in a coastal marine fish, the Spot Leiostomus xanthurus. We conducted a 90-d laboratory experiment in which treatment Spot were fed muscle of Blue Marlin Makaira nigricans with elevated concentrations of Hg mixed with a commercial fish food, while control Spot were fed only commercial food pellets. Gonadal maturation was induced by shortening the photoperiod and increasing the temperature. Spawning was induced by intramuscular injection of human chorionic gonadotropin at 100 IU/kg. Solid-sampling atomic absorption spectrophotometry measured the total Hg (THg), HgII, and MeHg in Blue Marlin muscle. Autometallography located Hg-sulfide granules in the liver, ovaries, and spawned eggs, and densitometry provided comparisons of Hg-sulfide granules in the ovaries of treatment and control Spot. Overall, the intensity and prevalence of Hg-sulfide granules were greater in the liver, ovaries, and eggs from treatment Spot than in those from controls. The tissue and cellular distribution of Hg-sulfide granules differed. Received November 18, 2016; accepted June 18, 2017.


Palliative Epineurotomy for Focal Radial Malignant Peripheral Nerve Sheath Tumor in a Dog.
This case report describes the diagnosis of a peripheral nerve sheath tumor of the deep branch of the radial nerve distal to the elbow in a dog. The lesion was identified using computed tomography and ultrasonography and confirmed as sarcoma on histopathological analysis of incisional biopsies. Clinical signs dramatically improved following surgical biopsy before recurring three months later. Repeat epineurotomy of the deep branch of the radial nerve resulted in clinical improvement for a further month before signs once again returned. Epineurotomy as a palliative treatment for peripheral nerve sheath tumors has not been previously described, but may have a place in palliation of clinical signs in specific cases of peripheral nerve sheath tumors in which limb amputation is not an option.


Organic farming and soil carbon sequestration: what do we really know about the benefits?
Organic farming is believed to improve soil fertility by enhancing soil organic matter (SOM) contents. An important co-benefit would be the sequestration of carbon from atmospheric CO2. Such a positive effect has been suggested based on data from field experiments though many studies were not designed to address the issue of carbon sequestration. The aim of our study was to examine published data in order to identify possible flaws such as missing a proper baseline, carbon mass measurements, or lack of a clear distinction between conventional and organic farming practices, thereby attributing effects of specific practices to organic farming, which are not uniquely organic. A total of 68 data sets were analyzed from 32 peer-reviewed publications aiming to compare conventional with organic farming. The analysis revealed that after conversion, soil C content (SOC) in organic systems increased annually by 2.2% on average, whereas in conventional systems SOC did not change significantly. The majority of publications reported SOC concentrations rather than amounts thus neglecting possible changes in soil bulk density. 34 out of 68 data sets missed a true control with well-defined starting conditions. In 37 out of 50 cases, the amount of organic fertilizer in the organic system exceeded that applied in the compared conventional system, and in half of the cases crop rotations differed between systems. In the few studies where crop rotation and organic fertilization were comparable in both systems no consistent difference in SOC was found. From this data analysis, we conclude that the claim for beneficial effects of organic farming on SOC is premature and that reported advantages of organic farming for SOC are largely determined by higher and often disproportionate application of organic fertilizer compared to conventional farming.


Immunological demonstration of Gq-protein in Limulus photoreceptors.
The phototransduction cascade in invertebrates involves the coupling of rhodopsin activation to the action of the enzyme phospholipase C. This step is performed by G-proteins. An antibody against the alpha-subunit of a mouse Gq type G-protein recognized protein bands in Western blots of lateral eye and ventral nerve photoreceptors of Limulus. The protein bands had an apparent molecular mass of about 42 kDa. The antibody also recognized protein bands of a similar molecular mass in immunoblots of brain and intestine tissue. Immunoreactivity was found in lateral eye frozen sections where it was confined to the rhabdom region. When the antibody was applied to ultrathin sections of ventral nerve photoreceptors, the highest density of labeling was found on the rhabdomeral microvilli, but gold particles were also scattered in the cytoplasm. We conclude that a G-protein of the type Gq participates in the phototransduction of Limulus.


Des-gamma-carboxy prothrombin in hepatocellular cancer patients waiting for liver transplant: a systematic review and meta-analysis.
The use of des-gamma-carboxy prothrombin (DCP) as a predictor of the risk of recurrence of hepatocellular cancer (HCC) after liver transplant (LT) has recently gained interest, especially in view of the recent extension of the eligibility criteria of these patients for LT. The aim of the present study is to look into this important matter based on a systematic review and meta-analysis. A systematic literature review about the role of DCP in the specific setting of LT for HCC has been conducted. Three selected studies, which showed a high rate of homogeneity (I2 = 0.0%), confirmed that the tumor marker DCP is a useful predictive factor, indicating a 5-fold increased risk for HCC recurrence after LT (p<0.001). The meta-analysis enabled us to underline the importance of DCP in the refinement of the eligibility criteria of HCC patients for LT. This information, based on Japanese studies performed in the setting of living-donor LT only, needs further validation in the Western world both in the setting of post-mortem and living-donor LT.


Clinical value of p53, c-erbB-2, CEA and CA125 regarding relapse, metastasis and death in resectable non-small cell lung cancer.
The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), loco-regional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung-cancer recurrence. They can add useful information regarding the complex nature of prognosis.


Long-term dry immersion: review and prospects.
Dry immersion, which is a ground-based model of prolonged conditions of microgravity, is widely used in Russia but is less well known elsewhere. Dry immersion involves immersing the subject in thermoneutral water covered with an elastic waterproof fabric. As a result, the immersed subject, who is freely suspended in the water mass, remains dry. For a relatively short duration, the model can faithfully reproduce most physiological effects of actual microgravity, including centralization of body fluids, support unloading, and hypokinesia. Unlike bed rest, dry immersion provides a unique opportunity to study the physiological effects of the lack of a supporting structure for the body (a phenomenon we call 'supportlessness'). In this review, we attempt to provide a detailed description of dry immersion. The main sections of the paper discuss the changes induced by long-term dry immersion in the neuromuscular and sensorimotor systems, fluid-electrolyte regulation, the cardiovascular system, metabolism, blood and immunity, respiration, and thermoregulation. The long-term effects of dry immersion are compared with those of bed rest and actual space flight. The actual and potential uses of dry immersion are discussed in the context of fundamental studies and applications for medical support during space flight and terrestrial health care.


Gene Positioning Effects on Expression in Eukaryotes.
The packaging and organization of the genome within the eukaryotic interphase nucleus directly influence how the genes are expressed. An underappreciated aspect of genome structure is that it is highly dynamic and that the physical positioning of a gene can impart control over its transcriptional status. In this review, we assess the current knowledge of how gene positioning at different levels of genome organization can directly influence gene expression during interphase. The levels of organization discussed include chromatin looping, topologically associated domains, chromosome territories, and nuclear compartments. We discuss specific studies demonstrating that gene positioning is a dynamic and highly regulated feature of the eukaryotic genome that allows for the essential spatiotemporal regulation of genes.


Sister chromatid exchanges in lymphocytes of humans anaesthetized with isoflurane.
The potential mutagenicity of isoflurane was investigated by the sister chromatid exchange (SCE) test using peripheral blood lymphocytes from patients before and after anaesthesia. Thirty patients, aged 18-59 yr (median 29.5 yr), were anaesthetized for minor orthopaedic operations with isoflurane and nitrous oxide in oxygen for 37-90 min (median 64 min). Venous blood samples were drawn before the induction of anaesthesia, immediately after completion of anaesthesia and on the following day. SCE was examined in 30 cells from each specimen. In the 30 patients, the SCE values observed immediately after completion of anaesthesia and the day after were not different statistically from the SCE values observed before the induction of anaesthesia. Separate statistical evaluation of SCE observed among the 19 non-smoking patients also revealed unchanged SCE values. In 11 cigarette-smoking patients (average 10 cigarettes per day), SCE was increased the day after operation when compared with SCE before the induction of anaesthesia (P less than 0.02). This might reflect differences in SCE formation attributable to the patients' smoking habits, but further studies of SCE in cigarette smokers are required to elucidate this. It was concluded that there was no indication, from the SCE test, of a mutagenic effect of short-term exposure to anaesthetic concentrations of isoflurane and nitrous oxide in oxygen.


NIFtHool: an informatics program for identification of NifH proteins using deep neural networks.
Atmospheric nitrogen fixation carried out by microorganisms has environmental and industrial importance, related to the increase of soil fertility and productivity. The present work proposes the development of a new high precision system that allows the recognition of amino acid sequences of the nitrogenase enzyme (NifH) as a promising way to improve the identification of diazotrophic bacteria. For this purpose, a database obtained from UniProt built a processed dataset formed by a set of 4911 and 4782 amino acid sequences of the NifH and non-NifH proteins respectively. Subsequently, the feature extraction was developed using two methodologies: (i) k-mers counting and (ii) embedding layers to obtain numerical vectors of the amino acid chains. Afterward, for the embedding layer, the data was crossed by an external trainable convolutional layer, which received a uniform matrix and applied convolution using filters to obtain the feature maps of the model. Finally, a deep neural network was used as the primary model to classify the amino acid sequences as NifH protein or not. Performance evaluation experiments were carried out, and the results revealed an accuracy of 96.4%, a sensitivity of 95.2%, and a specificity of 96.7%. Therefore, an amino acid sequence-based feature extraction method that uses a neural network to detect N-fixing organisms is proposed and implemented. NIFtHool is available from: https://nifthool.anvil.app/.


Genetic diversity between and within the arenavirus species indigenous to western Venezuela.
The results of analyses of Z, RNA-dependent RNA polymerase, glycoprotein precursor, and nucleocapsid protein gene sequence data suggested that Guanarito virus was the most common cause of Venezuelan hemorrhagic fever in a 7-year period in the 1990s and that the evolution of Pirital virus in association with Sigmodon alstoni (Alston's cotton rat) has occurred at a significantly higher rate than the evolution of Guanarito virus in association with Zygodontomys brevicauda (short-tailed cane mouse) on the plains of western Venezuela. The results of analyses of the primary structures of the glycoproteins of the 8 strains of Guanarito virus isolated from humans suggested that these strains would be highly cross-reactive in neutralization assays. Thus, passive antibody therapy may prove beneficial in the treatment of human disease caused by strains of Guanarito virus that are enzootic in the region in which Venezuelan hemorrhagic fever is endemic.


Humpback whale calls detected in tropical ocean basin between known Mexico and Hawaii breeding assemblies.
Humpback whales migrate in winter from northern feeding grounds to geographically separate breeding assemblies in near-shore waters of Mexico and Hawaii. Currently assessed as distinct populations warranting separate management, their shared song composition and interchange of photo-identified whales question this paradigm. To investigate a potential connection an autonomous Wave Glider performed a 6965.5 km, 100-day (round trip) acoustic survey from Hawaii toward Mexico circa 20° N, from January 15 to April 25, 2018. The 2272 h of recordings included humpback whale calls to approximately midway from Hawaii to Mexico. Explanations include an undocumented migration route, offshore assembly, or mid-season travel between assemblies.


Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?
Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1-6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD.


Governmental governance of host countries and cross-border merger and acquisition performance: Evidence from listed enterprises in China.
With globalization, the cases of Chinese enterprises' cross-border mergers and acquisitions (M&A) are increasing rapidly. The institutional environment of the host country has become an important factor influencing M&A performance, which has a profound impact on the success or failure of cross-border M&A. Based on this, for our study, we selected cases of cross-border M&A of listed companies in China from 2007 to 2018 as research samples to empirically test the impact of the host country's governance capacity on the cross-border M&A performance of acquirers. It was found that the host country's governance capacity has a negative effect on the M&A performance in the short term, but in the long term, it can effectively improve the cross-border M&A performance of acquirers. At the same time, specific to the relationship between the governmental governance capacity of six different dimensions and long-term M&A performance, the government effectiveness, regulation quality, and rule of law have the most significant promotional effect on long-term M&A performance. This implies that acquirers should focus on the long-term impact of governmental governance capacity on M&A, and consciously lean toward countries with strong governance capacity in order to obtain long-term value growth when arranging overseas M&A activities. The conclusion of this paper provides a reliable basis on which for companies to achieve sustainable growth in complex economic activities.


The potential of functionalized dressing releasing flavonoids facilitates scar-free healing.
Scars are pathological marks left after an injury heals that inflict physical and psychological harm, especially the great threat to development and aesthetics posed by oral and maxillofacial scars. The differential expression of genes such as transforming growth factor-β, local adherent plaque kinase, and yes-related transcriptional regulators at infancy or the oral mucosa is thought to be the reason of scarless regenerative capacity after tissue defects. Currently, tissue engineering products for defect repair frequently overlook the management of postoperative scars, and inhibitors of important genes alone have negative consequences for the organism. Natural flavonoids have hemostatic, anti-inflammatory, antioxidant, and antibacterial properties, which promote wound healing and have anti-scar properties by interfering with the transmission of key signaling pathways involved in scar formation. The combination of flavonoid-rich drug dressings provides a platform for clinical translation of compounds that aid in drug disintegration, prolonged release, and targeted delivery. Therefore, we present a review of the mechanisms and effects of flavonoids in promoting scar-free regeneration and the application of flavonoid-laden dressings.


Influence of optical surface distortion in a cylindrical Offner stretcher on the far-field signal-to-noise ratio.
In a stretcher, the surface distortion of the optical elements can introduce spectral phase modulations into the laser, which can affect the laser's signal-to-noise ratio. In this paper, by combining ray tracing methods and angular spectrum diffraction methods, the impact of the mid-frequency surface distortion of the optical elements in an cylindrical Offner stretcher on the far-field signal-to-noise ratio of the laser is simulated. The results show that reducing the spatial chirp on the convex cylindrical mirror can effectively improve the far-field signal-to-noise ratio of the laser, and two methods to improve the far-field signal-to-noise ratio are presented.


Operative diagnosis for revision total hip arthroplasty is associated with patient-reported outcomes (PROs).
Little is known about the impact of the reason for revision total hip arthroplasty (THA) on the outcomes following revision THA. In this study, our objective was to assess the association of operative diagnosis with patient-reported outcomes (PROs) after revision THA. We used prospectively collected data from the Mayo Clinic Total Joint Registry that collects pre- and post-operative pain and function outcomes using a validated Hip questionnaire, on all revision THAs from 1993-2005. We used logistic regression to assess the odds of moderate-severe index hip pain and moderate-severe limitation in activities of daily living (ADLs) 2- and 5-years after revision THA. We calculated odds ratios (OR) and 95% confidence intervals (CIs). For the 2- and 5-year cohorts, the operative diagnosis was loosening/wear/osteolysis in 73% and 75%; dislocation/bone or prosthesis fracture/instability or non-union in 17% and 15%; and failed prior arthroplasty with components removed/infection in 11% and 11%, respectively. In multivariable-adjusted analyses that included preoperative ADL limitations, compared to patients with loosening/wear/osteolysis, patients with dislocation/fracture/instability/non-union had OR of 2.2 (95% CI, 1.3-3.5; p = 0.002) for overall moderate-severe ADL limitation and those with failed prior arthroplasty/infection had OR of 1.6 (95% CI, 1.0-2.8; p = 0.06). At 5-years, ORs were lower and differences were no longer significant. Moderate-severe pain did not differ significantly by diagnosis, at 2- or 5-years in multivariable adjusted analyses, with one exception, i.e. failed prior arthroplasty/infection had a trend towards significance with odds ratio of 1.9 (95% CI, 0.9-3.8; p = 0.07). Operative diagnosis is independently associated with ADL limitations, but not pain, at 2-years after revision THA. Patients should be informed of the risk of poorer short-term outcomes based on their diagnosis.


Production and characterization of PHB-HV copolymer by Bacillus thuringiensis isolated from Eisenia foetida.
Polyhydroxyalkanoates (PHAs) are one of the most important biopolyesters produced by vast number of microorganisms that exist in the environment. PHAs gained much attention due to its inherent biodegradable and biocompatible ability along with its physicochemical properties, which are similar to those of conventional petroleum-based plastics. In the present study, PHA producing bacterial strains was isolated from earthworm. Initially, four bacterial strains were selected based on the intensity of fluorescence from 80 non-clonal isolates. Bacillus thuringiensis (B.t.) E101 was identified as the bacterium producing highest yield of PHA (3.6 ± 0.04 g L-1 ) through biochemical and molecular techniques such as 16S rRNA gene sequence analysis. Growth parameters such as carbon, nitrogen sources, and incubation time were optimized with respect to higher PHA production. Both qualitative (Fourier transform infrared spectroscopy and nuclear magnetic resonance) and quantitative (GC-MS) characterizations revealed that the polymer produced by B.t.E101 contains the characteristic peaks for poly(3-hydroxybutyrate-co-3-hydroxyvalerate) copolymer. This is the first report for the occurrence, successful isolation, and characterization of PHA producing Bacillus sp. from earthworm.


Phospho-ΔNp63α/microRNA network modulates epigenetic regulatory enzymes in squamous cell carcinomas.
The tumor protein (TP) p63/microRNAs functional network may play a key role in supporting the response of squamous cell carcinomas (SCC) to chemotherapy. We show that the cisplatin exposure of SCC-11 cells led to upregulation of miR-297, miR-92b-3p, and miR-485-5p through a phosphorylated ΔNp63α-dependent mechanism that subsequently modulated the expression of the protein targets implicated in DNA methylation (DNMT3A), histone deacetylation (HDAC9), and demethylation (KDM4C). Further studies showed that mimics for miR-297, miR-92b-3p, or miR-485-5p, along with siRNA against and inhibitors of DNMT3A, HDAC9, and KDM4C modulated the expression of DAPK1, SMARCA2, and MDM2 genes assessed by the quantitative PCR, promoter luciferase reporter, and chromatin immunoprecipitation assays. Finally, the above-mentioned treatments affecting epigenetic enzymes also modulated the response of SCC cells to chemotherapeutic drugs, rendering the resistant SCC cells more sensitive to cisplatin exposure, thereby providing the groundwork for novel chemotherapeutic venues in treating patients with SCC.


Genetic diversity and population structure among six cattle breeds in South Africa using a whole genome SNP panel.
Information about genetic diversity and population structure among cattle breeds is essential for genetic improvement, understanding of environmental adaptation as well as utilization and conservation of cattle breeds. This study investigated genetic diversity and the population structure among six cattle breeds in South African (SA) including Afrikaner (n = 44), Nguni (n = 54), Drakensberger (n = 47), Bonsmara (n = 44), Angus (n = 31), and Holstein (n = 29). Genetic diversity within cattle breeds was analyzed using three measures of genetic diversity namely allelic richness (AR), expected heterozygosity (He) and inbreeding coefficient (f). Genetic distances between breed pairs were evaluated using Nei's genetic distance. Population structure was assessed using model-based clustering (ADMIXTURE). Results of this study revealed that the allelic richness ranged from 1.88 (Afrikaner) to 1.73 (Nguni). Afrikaner cattle had the lowest level of genetic diversity (He = 0.24) and the Drakensberger cattle (He = 0.30) had the highest level of genetic variation among indigenous and locally-developed cattle breeds. The level of inbreeding was lower across the studied cattle breeds. As expected the average genetic distance was the greatest between indigenous cattle breeds and Bos taurus cattle breeds but the lowest among indigenous and locally-developed breeds. Model-based clustering revealed some level of admixture among indigenous and locally-developed breeds and supported the clustering of the breeds according to their history of origin. The results of this study provided useful insight regarding genetic structure of SA cattle breeds.


A Highly Sensitive and Stable rGO:MoS2-Based Chemiresistive Humidity Sensor Directly Insertable to Transformer Insulating Oil Analyzed by Customized Electronic Sensor Interface.
Reduced graphene oxide and molybdenum disulfide (rGO:MoS2) are the most representative two-dimensional materials, which are promising for a humidity sensor owing to its high surface area, a large number of active sites, and excellent mechanical flexibility. Herein, we introduced a highly sensitive and stable rGO:MoS2-based humidity sensor integrated with a low-power in-plane microheater and a temperature sensor, directly insertable to transformer insulating oil, and analyzed by a newly developed customized sensor interface electronics to monitor the sensor's output variations in terms of relative humidity (RH) concentration. rGO:MoS2 sensing materials were synthesized by simple ultrasonication without using any additives or additional heating and selectively deposited on titanium/platinum (Ti/Pt) interdigitated electrodes on a SiO2 substrate using the drop-casting method. The significant sensing capability of p-n heterojunction formation between rGO and MoS2 was observed both in the air and transformer insulating oil environment. In air testing, the sensor exhibited an immense sensitivity of 0.973 kΩ/%RH and excellent linearity of ∼0.98 with a change of humidity from 30 to 73 %RH, and a constant resistance deviation with an inaccuracy rate of 0.13% over 400 h of continual measurements. In oil, the sensor showed a high sensitivity of 1.596 kΩ/%RH and stable repeatability for an RH concentration range between 34 and 63 %RH. The obtained results via the sensor interface were very similar to those measured with a digital multimeter, denoting that our developed total sensor system is a very promising candidate for real-time monitoring of the operational status of power transformers.


Synthetic exploration of electrophilic xanthylation via powerful N-xanthylphthalimides.
Organic xanthates are broadly applied as synthetic intermediates and bioactive molecules in synthetic chemistry. Electrophilic xanthylation represents a promising approach but has rarely been explored mainly due to the lack of powerful electrophilic reagents. Herein, synthetic exploration of electrophilic xanthylation via powerful N-xanthylphthalimides was investigated. This strategy might provide a new avenue to less-concerned but meaningful electrophilic xanthylation in organic synthesis. With the help of these powerful reagents, electrophilic xanthylation of a wide range of substrates including aryl/alkenyl boronic acids, β-keto esters, 2-oxindole, and alkyl amines, as well as previously inaccessible phenols (first report) was achieved under mild reaction conditions. Notably, this simple electrophilic xanthylation of alkyl amine substrates will occur in the desulfuration reaction, consistent with the previously reported methods. Similarly, xanthamide and thioxanthate groups could also be transformed into desired nucleophiles via this electrophilic reagent strategy. The broad substrate scope, excellent functional group compatibility and late-stage functionalization of bioactive or functional molecules made them very attractive as general reagents which will allow rapid incorporation of SC(S)R (R = OEt, Oalkyl, NEt2 and SEt) into the target molecules.


Cholesterol Crystal Embolism and Chronic Kidney Disease.
Renal disease caused by cholesterol crystal embolism (CCE) occurs when cholesterol crystals become lodged in small renal arteries after small pieces of atheromatous plaques break off from the aorta or renal arteries and shower the downstream vascular bed. CCE is a multisystemic disease but kidneys are particularly vulnerable to atheroembolic disease, which can cause an acute, subacute, or chronic decline in renal function. This life-threatening disease may be underdiagnosed and overlooked as a cause of chronic kidney disease (CKD) among patients with advanced atherosclerosis. CCE can result from vascular surgery, angiography, or administration of anticoagulants. Atheroembolic renal disease has various clinical features that resemble those found in other kidney disorders and systemic diseases. It is commonly misdiagnosed in clinic, but confirmed by characteristic renal biopsy findings. Therapeutic options are limited, and prognosis is considered to be poor. Expanding knowledge of atheroembolic renal disease due to CCE opens perspectives for recognition, diagnosis, and treatment of this cause of progressive renal insufficiency.


Genetic control of alternative splicing in the TAP2 gene: possible implication in the genetics of type 1 diabetes.
The transporter 2, ATP-binding cassette, subfamily B (TAP2) is involved in the transport of antigenic peptides to HLA molecules. Coding TAP2 polymorphisms shows a strong association with type 1 diabetes, but it is not clear whether this association may be entirely due to linkage disequilibrium with HLA DR and DQ. Functionally, rat Tap2 nonsynonymous single-nucleotide polymorphisms (nsSNPs) confer differential selectivity for antigenic peptides, but this was not shown to be the case for human TAP2 nsSNPs. In the human, differential peptide selectivity is rather conferred by two splicing isoforms with alternative carboxy terminals. Here, we tested the hypothesis that alleles at the coding SNPs favor different splicing isoforms, thus determining peptide selectivity indirectly. This may be the basis for independent contribution to the type 1 diabetes association. In RNA from heterozygous lymphoblastoid lines, we measured the relative abundance of each SNP haplotype in each isoform. In isoform NM_000544, the G (Ala) allele at 665 Thr>Ala (rs241447) is more than twice as abundant as A (Thr) (GA = 2.2 +/- 0.4, P = 1.5 x 10(-4)), while isoform NM_018833 is derived almost exclusively from chromosomes carrying A (AG = 18.1 +/- 5.6, P = 2.04 x 10(-7)). In 889 Canadian children with type 1 diabetes, differential transmission of parental TAP2 alleles persisted (P = 0.011) when analysis was confined to chromosomes carrying only DQ*02 alleles, which mark a conserved DR-DQ haplotype, thus eliminating most of the variation at DR-DQ. Thus, we present evidence of TAP2 association with type 1 diabetes that is independent of HLA DR-DQ and describe a plausible functional mechanism based on allele dependence of splicing into isoforms known to have differential peptide selectivities.


Staged treatment of high energy midfoot fracture dislocations.
Staged care with interval external fixation is a successful established treatment strategy for high energy periarticular fractures with often extensive soft tissue damage such as the tibial plateau and plafond. The aim of the current study was to determine whether staged care of high energy midfoot fracture/dislocation with interval external fixation prior to definitive open reconstruction in the polytraumatized patient was both safe and efficacious. One hundred twenty-three patients were operated on for high energy midfoot fracture/dislocation during the 8-year study period. Eighteen polytrauma patients were selectively treated with a staged protocol. Radiographic assessment was utilized to determine if the fixator achieved gross skeletal alignment. Further, final alignment after definitive reconstruction and postoperative complications were analyzed. The fixator improved both length and alignment of all high energy midfoot fracture/dislocations. Loss of acceptable reduction while in the temporary frame occurred in only 1 case. Final alignment after definitive reconstruction was anatomic in all cases. No cases of wound-related complication and/or deep infection occurred. Delayed reconstruction of high energy midfoot fracture/dislocation using interval external fixation should be an accepted care paradigm in selected polytrauma patients. Level III, retrospective comparative study.


R-roscovitine reduces lung inflammation induced by lipoteichoic acid and Streptococcus pneumoniae.
Bacterial pneumonia remains associated with high morbidity and mortality. The gram-positive pathogen Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. Lipoteichoic acid (LTA) is an important proinflammatory component of the gram-positive bacterial cell wall. R-roscovitine, a purine analog, is a potent cyclin-dependent kinase (CDK)-1, -2, -5 and -7 inhibitor that has the ability to inhibit the cell cycle and to induce polymorphonuclear cell (PMN) apoptosis. We sought to investigate the effect of R-roscovitine on LTA-induced activation of cell lines with relevance for lung inflammation in vitro and on lung inflammation elicited by either LTA or viable S. pneumoniae in vivo. In vitro R-roscovitine enhanced apoptosis in PMNs and reduced tumor necrosis factor (TNF)-α and keratinocyte chemoattractant (KC) production in MH-S (alveolar macrophage) and MLE-12/MLE-15 (respiratory epithelial) cell lines. In vivo R-roscovitine treatment reduced PMN numbers in bronchoalveolar lavage fluid during LTA-induced lung inflammation; this effect was reversed by inhibiting apoptosis. Postponed treatment with R-roscovitine (24 and 72 h) diminished PMN numbers in lung tissue during gram-positive pneumonia; this step was associated with a transient increase in pulmonary bacterial loads. R-roscovitine inhibits proinflammatory responses induced by the gram-positive stimuli LTA and S. pneumoniae. R-roscovitine reduces PMN numbers in lungs upon LTA administration by enhancing apoptosis. The reduction in PMN numbers caused by R-roscovitine during S. pneumoniae pneumonia may hamper antibacterial defense.


A case report of hepatopulmonary syndrome in hereditary hemorrhagic telangiectasia (HHT): Not all right-to-left shunting in HHT is due to pulmonary arteriovenous malformations.
Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by abnormal vessel growth that results in telangiectasias and arteriovenous malformations (AVMs) in the skin, mucosa, and viscera. Up to 30% of patients with HHT exhibit pulmonary AVMs (PAVMs), clinically manifesting as right-to-left shunting and hypoxemia. We report an unusual and novel case of a patient with HHT who lacked clinical sequelae of portal hypertension but presented to clinic with hypoxemia without dyspnea. Diagnostic workup revealed noncardiac right-to-left shunting due to hepatopulmonary syndrome (HPS) from HHT-induced portal hypertension rather than PAVMs. The diagnosis was confirmed by the absence of PAVMs on chest computed tomography and evidence of elevated portal pressures as noted by the presence of small esophageal varices on upper endoscopy and histologic findings on liver biopsy. Due to the patient's mild symptoms, no further intervention was required. He was closely followed up in the outpatient setting for changes in symptoms and underwent annual screening for development of PAVMs. The patient continues to do well clinically. He has not experienced worsening hypoxemia or dyspnea and has not developed PAVMs. Given that management of hypoxemia in HPS drastically differs from that of hypoxemia due to PAVMs, this case demonstrates the importance of evaluating HHT patients for HPS if they exhibit impaired oxygenation and noncardiac right-to-leftshunting in the setting of hepatic arteriovenous shunting.


Macroscopic Graphene Fibers Directly Assembled from CVD-Grown Fiber-Shaped Hollow Graphene Tubes.
Using a copper wire as the substrate for the CVD growth of a hollow multilayer graphene tube, we prepared a macroscopic porous graphene fiber by removing the copper in an aqueous mixture solution of iron chloride (FeCl3, 1 M) and hydrochloric acid (HCl, 3 M) and continuously drawing the newly released graphene tube out of the liquid. The length of the macroscopic graphene fiber thus produced is determined mainly by the length of the copper wire used. The resultant macroscopic graphene fiber with the integrated graphene structure exhibited a high electrical conductivity (127.3 S cm(-1)) and good flexibility over thousands bending cycles, showing great promise as flexible electrodes for wearable optoelectronics and energy devices-exemplified by its use as a flexible conductive wire for lighting a LED and a cathode in a fiber-shaped dye-sensitized solar cell (DSSC) with one of the highest energy conversion efficiencies (3.25%) among fiber-shaped DSSCs.


Disrupting Glutamate Co-transmission Does Not Affect Acquisition of Conditioned Behavior Reinforced by Dopamine Neuron Activation.
Dopamine neurons in the ventral tegmental area (VTA) were previously found to express vesicular glutamate transporter 2 (VGLUT2) and to co-transmit glutamate in the ventral striatum (VStr). This capacity may play an important role in reinforcement learning. Although it is known that activation of the VTA-VStr dopamine system readily reinforces behavior, little is known about the role of glutamate co-transmission in such reinforcement. By combining electrode recording and optogenetics, we found that stimulation of VTA dopamine neurons in vivo evoked fast excitatory responses in many VStr neurons of adult mice. Whereas conditional knockout of the gene encoding VGLUT2 in dopamine neurons largely eliminated fast excitatory responses, it had little effect on the acquisition of conditioned responses reinforced by dopamine neuron activation. Therefore, glutamate co-transmission appears dispensable for acquisition of conditioned responding reinforced by DA neuron activation.


Effects of Selective M1 Muscarinic Receptor Activation on Hippocampal Spatial Representations and Neuronal Oscillations.
The muscarinic M1 acetylcholine receptor is a key target for drugs aimed at treating cognitive dysfunction, including the memory impairment in Alzheimer's disease. The overall question of the current study was to ask how systemic administration of the bitopic M1 agonist VU0364572, the M1 positive allosteric modulator BQCA, and the acetylcholinesterase inhibitor donepezil (current standard of care for Alzheimer's disease), would impact spatial memory-related hippocampal function in rats. Hippocampal pyramidal neuron spiking and local field potentials were recorded from regions CA1 and CA3 as rats freely foraged in a recording enclosure. To assess the relative stability versus flexibility of the rats' spatial representations, the walls of the recording enclosure were reshaped in 15-m intervals. As compared to the control condition, systemic administration of VU0364572 increased spatial correlations of CA1 and CA3 pyramidal neuron spiking across all enclosure shape comparisons, whereas BQCA and donepezil appeared to decrease these spatial correlations. Further, both VU0364572 and BQCA increased intrahippocampal synchrony as measured by CA3-CA1 field-field coherence in frequency ranges that tended to align with the prominence of those oscillations for the behavioral state (i.e., theta during locomotion and slow gamma during stationary moments). The results indicated that VU0364572 and BQCA influenced hippocampal function differently but in ways that might both be beneficial for treating memory dysfunction.


Androgen receptors in two androgen-mediated, sexually dimorphic characters of frogs.
The presence/absence of androgen receptors is examined in two sexually dimorphic features of frogs: the nuptial pad and the external oblique muscle. Immunohistochemistry reveals that both males and females possess androgen receptors in these tissues. Males have a higher density of immunopositive nuclei in the oblique muscle than do females. The presence of androgen receptors in both male and female tissues is consistent with results from hormone experiments in which androgen supplements induce the expression of a nuptial pad and enlarge the external oblique muscles in castrated males and ovariectomized females.


[Cholestasis in pregnancy].
The authors report the main morphological and functional alterations of the liver during the course of pregnancy. The size of the organ does not change and there is a slight (20%) reduction of hepatic flow. Hepatic function is partially modified in view of the following factors: reduced protein synthesis (in particular the albumin component), increased serum levels of cholesterol and triglycerides mediated by steroid hormones, inhibition of canalicular secretion and consequent diminution of the liver's excretory function, variations in serum levels of many markers of cholestasis so much so that they become unreliable due to pregnancy. The high level of sexual steroids also influences cholecystic kinetics: progesterone, in particular, negatively affects the contractile response to cholecystokinin-pancreozymin stimulus. The paper then reports some historical data including those which led to the definition of "gravidic cholestasis" as a clinical condition. The incidence of the disease varies considerably in relation to the geographical area and genetic factors. In Sweden and Finland the percentage ranges between 1 and 3%, whereas much higher values (12-22%) are reported in Chile and among the American Indians. The latest data for Italy reveal an incidence of 0.34%. The onset of disease is conditioned by familial predisposition due to an enhanced sensitivity to estrogens or excessive production of estrogenic metabolites. Among the hepatocytic changes induced by estrogens are the reduced fluidity of sinusoidal plasmatic membranes and the inhibition of vasolateral Na+K+ ATPase pump activity. The last months of gestation are characterized by a "cholestatic state" which may vary in severity from slight symptoms, to itching and idiopathic jaundice.(ABSTRACT TRUNCATED AT 250 WORDS)


The impacts of C-reactive protein and atrial fibrillation on carotid atherosclerosis and ischemic stroke in patients with suspected ischemic cerebrovascular disease: a single-center retrospective observational cohort study.
Carotid intima-media thickness (IMT) is associated with chronic inflammation, and C-reactive protein (CRP) level is elevated in patients with atrial fibrillation (AF). We investigated the impacts of CRP and AF on carotid atherosclerosis and ischemic stroke in patients with suspected ischemic cerebrovascular disease. One-hundred forty patients (78 males) with suspected ischemic cerebrovascular disease underwent carotid ultrasonography. The mean common carotid artery IMT, mean internal carotid artery (ICA) IMT, and plaque score were measured. Patients were divided into four groups according to the presence of AF and elevated CRP level {n=46 for AF(-)CRP(-), n=38 for AF(-)CRP(+), n=43 for AF(+)CRP(-), and n=13 for AF(+)CRP(+)}. Common carotid artery IMT was significantly higher in the AF(-)CRP(+) (0.98±0.51 mm) and AF(+)CRP(+) (0.96±0.27 mm) groups compared to the AF(-)CRP(-) (0.80±0.32 mm) and AF(+)CRP(-) (0.77±0.19 mm) groups (p=0.027). Although there was no significant difference in mean ICA IMT among the groups, plaque score was the highest in the AF(+)CRP(+) (4.18±3.84 mm) group, followed by AF(-)CRP(+) (3.87±2.78 mm), AF(+)CRP(-) (1.34±2.61 mm), and AF(-)CRP(-) (1.17±2.02 mm) (p<0.001). The AF(+)CRP(+) group showed significantly higher incidence of ischemic stroke than the other groups (all p<0.05). Binary logistic regression analysis showed that age {odds ratio (OR)=1.033, p=0.001}, elevated CRP (OR=3.884, p=0.001), and the presence of AF (OR=1.375, p=0.018) were significantly correlated with incidence of ischemic stroke. Elevated plasma CRP concentration may be a reliable surrogate marker for predicting carotid atherosclerosis in patients with AF, which may be related to increased risk of ischemic stroke.


Studies of folded peptide-based catalysts for asymmetric organic synthesis.
Folded peptides have proven to be a fertile area for discovery of catalysts for reactions in organic synthesis. Both combinatorial chemistry and rational design have fueled these discoveries. In both lines of research, mechanistic studies following the discovery of selective reactions have led to structural information that has stimulated attempts to correlate peptide structure and the relay of stereochemical information. Thus, key elements of the design of peptide-based catalysts include the identification of catalytically competent functional groups and their incorporation into three-dimensional structures that provide an appropriate chiral environment. Of note, turns, helices, nonobvious folds, and still undetermined secondary structures characterize the structural and functionally diverse motifs that enable peptide-catalyzed asymmetric reactions to occur.


Differences in 5-HT2A and mGlu2 Receptor Expression Levels and Repressive Epigenetic Modifications at the 5-HT2A Promoter Region in the Roman Low- (RLA-I) and High- (RHA-I) Avoidance Rat Strains.
The serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptors regulate each other and are associated with schizophrenia. The Roman high- (RHA-I) and the Roman low- (RLA-I) avoidance rat strains present well-differentiated behavioral profiles, with the RHA-I strain emerging as a putative genetic rat model of schizophrenia-related features. The RHA-I strain shows increased 5-HT2A and decreased mGlu2 receptor binding levels in prefrontal cortex (PFC). Here, we looked for differences in gene expression and transcriptional regulation of these receptors. The striatum (STR) was included in the analysis. 5-HT2A, 5-HT1A, and mGlu2 mRNA and [3H]ketanserin binding levels were measured in brain homogenates. As expected, 5-HT2A binding was significantly increased in PFC in the RHA-I rats, while no difference in binding was observed in STR. Surprisingly, 5-HT2A gene expression was unchanged in PFC but significantly decreased in STR. mGlu2 receptor gene expression was significantly decreased in both PFC and STR. No differences were observed for the 5-HT1A receptor. Chromatin immunoprecipitation assay revealed increased trimethylation of histone 3 at lysine 27 (H3K27me3) at the promoter region of the HTR2A gene in the STR. We further looked at the Akt/GSK3 signaling pathway, a downstream point of convergence of the serotonin and glutamate system, and found increased phosphorylation levels of GSK3β at tyrosine 216 and increased β-catenin levels in the PFC of the RHA-I rats. These results reveal region-specific regulation of the 5-HT2A receptor in the RHA-I rats probably due to absence of mGlu2 receptor that may result in differential regulation of downstream pathways.


Solid-phase synthesis of alkanethiols for the preparation of self-assembled monolayers.
Self-assembled monolayers (SAMs) of alkanethiols (ATs) on gold can be used to fabricate surfaces for nanoscience and biology. The chemical structure of the interface can be tailored simply by modifying the AT headgroup. To streamline access to different precursor ATs, we developed a general solid-phase synthetic route. A key feature of this route is the use of a modified resin containing an AT linker ("AT resin") because it minimizes purification steps. The precursor to the AT resin was prepared in five steps, and all of the synthetic intermediates are stable solids that can be purified by crystallization. Accordingly, the AT resin can be prepared on a multigram scale. The utility of the AT resin was evaluated by using it to generate a variety of ATs. For example, ATs presenting different types of integrin-binding ligands (linear and cyclic RGD derivatives) were prepared and used to form arrays of SAMs that support cell adhesion. Additionally, the AT resin also provides a starting point for the synthesis of ATs presenting reactive groups (e.g., an amine-reactive AT or a maleimide-containing alkanedisulfide) or protein immobilization tags (e.g., biotin-AT). Thus, our synthetic strategy provides a convenient and flexible means for the synthesis of the necessary building blocks for custom SAMs and SAM arrays.


Safety of Striatal Infusion of siRNA in a Transgenic Huntington's Disease Mouse Model.
The immune system In Huntington's disease (HD) is activated and may overreact to some therapies. RNA interference using siRNA lowers mutant huntingtin (mHTT) protein but could increase immune responses. To examine the innate immune response following siRNA infusion into the striatum of wild-type (WT) and HD transgenic (YAC128) mice. siRNAs (2'-O-methyl phosphorothioated) were infused unilaterally into striatum of four month-old WT and YAC128 mice for 28 days. Microglia number and morphology (resting (normal), activated, dystrophic), cytokine levels, and DARPP32-positive neurons were measured in striatum immediately or 14 days post-infusion. Controls included contralateral untreated striatum, and PBS and sham treated striata. The striata of untreated YAC128 mice had significantly fewer resting microglia and more dystrophic microglia than WT mice, but no difference from WT in the proportion of activated microglia or total number of microglia. siRNA infusion increased the total number of microglia in YAC128 mice compared to PBS treated and untreated striata and increased the proportion of activated microglia in WT and YAC128 mice compared to untreated striata and sham treated groups. Cytokine levels were low and siRNA infusion resulted in only modest changes in those levels. siRNA infusion did not change the number of DARPP32-positive neurons. Findings suggest that siRNA infusion may be a safe method for lowering mHTT levels in the striatum in young animals, since treatment does not produce a robust cytokine response or cause neurotoxicity. The potential long-term effects of a sustained increase in total and activated microglia after siRNA infusion in HD mice need to be explored.


Automatic ICD Code Assignment based on ICD's Hierarchy Structure for Chinese Electronic Medical Records.
Medical records are text documents recording diagnoses, symptoms, examinations, etc. They are accompanied by ICD codes (International Classification of Diseases). ICD is the bedrock for health statistics, which maps human condition, injury, disease etc. to codes. It has enormous financial importance from public health investment to health insurance billing. However, assigning codes to medical records normally needs a lot of human labour and is error-prone due to its complexity. We present a 3-layer attentional convolutional network based on the hierarchy structure of ICD code that predicts ICD codes from medical records automatically. The method shows high performance, with Hit@1 of 0.6969, and Hit@5 of 0.8903, which is better than state-of-the-art method.


Behaviour of the duct-ligated canine pancreas during hypothermic albumin perfusion.
The behaviour of eight duct-ligated canine pancreata was studied during 23 hours of continuous, hypothermic perfusion, with an albumin electrolyte solution. The organs developed a considerable oedema during perfusion. This did not seem to influence on the vascular resistance of the organs. A continuous insulin release, a moderate increase in LDH concentration and only small changes in the electrolyte concentrations were observed in the perfusate, indicating only a moderate degree of cellular damage.


A perspective on life-cycle health technology assessment and real-world evidence for precision oncology in Canada.
Health technology assessment (HTA) can be used to make healthcare systems more equitable and efficient. Advances in precision oncology are challenging conventional thinking about HTA. Precision oncology advances are rapid, involve small patient groups, and are frequently evaluated without a randomized comparison group. In light of these challenges, mechanisms to manage precision oncology uncertainties are critical. We propose a life-cycle HTA framework and outline supporting criteria to manage uncertainties based on real world data collected from learning healthcare systems. If appropriately designed, we argue that life-cycle HTA is the driver of real world evidence generation and furthers our understanding of comparative effectiveness and value. We conclude that life-cycle HTA deliberation processes must be embedded into healthcare systems for an agile response to the constantly changing landscape of precision oncology innovation. We encourage further research outlining the core requirements, infrastructure, and checklists needed to achieve the goal of learning healthcare supporting life-cycle HTA.


Errors and uncertainties in external radiation therapy. A system analysis with a cell kinetic model.
The relative importance of accurate knowledge and control of various biologic and physical factors in external radiation therapy was estimated with a simple cell kinetic treatment response model for a simulated tumour therapy situation. A set of parameter values was chosen for a reference case so that the calculated probability of zero surviving tumour cells was about 0.5. The parameters were varied, one at a time, over a range that was considered representative with respect to uncertainty in dose calculation, dose delivery and the description of the pertinent patient data. Also parameters in the cell kinetic model were varied. The calculations demonstrated a strong influence on the number of surviving cells from even moderate changes in the parameters which affect the tumour dose. Predictions with regard to curability are heavily dependent on the reliability of the biologic parameters in the model.


Strategy for allergenicity assessment of 'natural novel foods': clinical and molecular investigation of exotic vegetables (water spinach, hyacinth bean and Ethiopian eggplant).
Foods not commonly consumed in the European Union must be proven safe before being brought to market, including an assessment of allergenicity. We present a three-stepwise strategy for allergenicity assessment of natural novel foods using three novel vegetables, namely, water spinach, hyacinth bean, Ethiopian eggplant. First, vegetable extracts were analyzed for the presence of pan-allergens [Bet v 1 homologous proteins, profilins, nonspecific lipid transfer proteins (LTP)] by immunoblot analysis with specific animal antibodies. Secondly, the IgE-binding of the food extracts was investigated by EAST (Enzyme-allergosorbent test) and immunoblot analysis using sera with IgE-reactivity to known pan-allergens or to phylogenetically related foods from subjects (i) allergic to birch, grass and mugwort pollen, (ii) with food allergy to soy, peanut, tomato, multiple pollen-related foods and (iii) sensitized to LTP. Thirdly, the clinical relevance of IgE-binding was assessed in vivo by skin prick testing (SPT) and open oral food challenges (OFC). Profilin and LTP were detected by animal antibodies in all vegetables, a Bet v 1 homologue selectively in hyacinth bean. IgE-binding to LTP, profilin and a Bet v 1 homologue was proven by immunoblot analysis and EAST. Positive SPT and OFC results were observed for all vegetables in pollen-allergic patients. Our stepwise procedure confirmed the presence and IgE-binding capacity of novel vegetable proteins homologous to known allergens in endemic vegetable foods. In vivo testing proved the potential of the novel vegetables to elicit clinical allergy. Hence, our described algorithm seems to be applicable for allergenicity testing of natural novel foods.


Improved stability of methanolic Wright's stain solution with dual additives.
Degradation of methanolic Wright's stain solutions was greatly diminished with the addition of diethylamine hydrochloride and dimethylamine hydrochloride as costabilizers. Precipitation problems were eliminated by the dual additives. The stabilized stain solutions demonstrated good staining performance on blood smears. Methods for predicting the shelf life using calculated analytical parameters are described. Using these methods, the shelf life of a control stain solution was predicted to be 0.7 years; predicted shelf life was more than tripled with the addition of diethylamine hydrochloride and was increased approximately 27 times with the addition of both diethylamine hydrochloride and dimethylamine hydrochloride.


Epidemiologic aspects of elderly hypertensive patients and the results of treatment with nitrendipine.
Throughout the developed world, populations are growing older. Blood pressure, especially systolic blood pressure, increases with aging, and this increase leads to increased risks of cardiovascular morbidity and mortality. Clinical trials demonstrate that treatment of hypertension in the elderly reduces overall cardiovascular mortality, cardiac mortality, nonfatal cardiovascular events, congestive heart failure, progression to severe hypertension, and strokes. Drug treatment has been well tolerated, but diuretic therapy has been known to increase plasma glucose, uric acid, and creatinine. Therapeutic trials of nonpharmacologic treatment may be indicated in those with mild elevation in blood pressure and no serious end organ disease. However, most people up to age 80 will require drug treatment. Many drugs are effective in the elderly, but, some like beta-blockers, may not be as effective as in younger patients. Controlled clinical trials demonstrate that nitrendipine, a calcium channel blocking drug, significantly reduced mean systolic and diastolic blood pressure in older hypertensive patients, (successfully controlling pressure in a high percentage) and was well tolerated. Drug effects persist for 12 h or more. The drug decreased the exercise-induced rise in the rate-pressure product. Although there is a temporary increase in heart rate, this returns to baseline after a short time. Side effects include headache, flushing, dizziness, edema, and palpitations. Therefore, nitrendipine offers a reasonable and useful alternative to many other drugs in the treatment of combined systolic and diastolic hypertension in the elderly.


A novel pyrrolidonoalkaneamine (WR268954) that modulates chloroquine resistance of Plasmodium falciparum in vitro.
With the recent observations of efflux of chloroquine from Plasmodium falciparum and modulation of chloroquine resistance by calcium channel blockers, such as verapamil, a great deal of attention has been focused on the development of new modulators that can potentiate the efficacy of chloroquine. We report a new compound, WR268954, that has weak intrinsic antimalarial activity compared to chloroquine. In vitro, it increased the susceptibilities of chloroquine-resistant P. falciparum strains to chloroquine and quinine, but did not affect the chloroquine-susceptible strains. In the presence of 2,000 nM of WR268954, the 50% inhibitory concentration of chloroquine for drug-resistant P. falciparum decreased 90-fold in comparison with the control (chloroquine only). The same concentration of WR268954 increased the potentiation of chloroquine in resistant strains to a level approximately equivalent to that observed for the sensitive strain. This compound also potentiates the efficacy of quinine in drug-resistant parasites. However, WR268954 did not enhance the efficacy of mefloquine in the mefloquine-resistant parasites. In this report, the data show the synergistic effect of WR268954 on the antimalarial activity of chloroquine in drug-resistant strains of P. falciparum, but only an additive effect on drug-sensitive strains of parasites. Compound WR268954 belongs to a pyrrolidino alkane amine class whose in vitro chloroquine resistance modulator activity supports the basis for the synthesis of this class of compounds.


[Use of direct magnification technic of the hand radiograph in children with chronic renal insufficiency].
The characteristic changes of renal osteopathy in the hand are shown by the X-rays of seven children with end stage renal disease using the direct magnification technique. All children had pathologic conditions in the hands. Most frequently tunnelation , spiculae in the phalanges and metaphyseal translucent bands in the forearm were seen. Less constantly acroosteolyses and generalized osteoporosis could be observed. The X-rays of the hands using the direct magnification technique with rare earth film-screen system and a microfocus X-ray tube are sufficient to determine renal osteopathy. If clinical symptoms are present, X-rays of other parts of the skeleton are necessary. By using the above mentioned radiologic technique the radiographic diagnostic effort could be minimized.


Clinicopathologic features of six cases of primary cervical lymphoma.
Primary lymphoma of the uterine cervix is rare, with less than 60 cases reported. We present a series of 6 patients with cervical lymphoma and review the literature. Between 1988 and 2003, we identified 6 women with primary lymphoma of the uterine cervix treated at our institutions. Data for analysis were obtained from hospital charts, office records, and tumor registry files. We also reviewed 20 published reports on cervical lymphoma, providing information on 58 additional patients. The median age at diagnosis was 52 years (range 40-76). Three patients had an abnormal Papanicolaou test within 6 months of the diagnosis. Mean tumor size was 8.3 cm (range 3-14 cm). On the basis of the Ann Arbor system of staging where "E" denotes extranodal tumor origin, 2 patients had stage IE, 1 had stage IIIE, and 3 had stage IVE disease. The median follow-up for these 6 women was 33 months (range 12-120). Adding the 6 patients in our series to the 58 patients obtained from published reports, 43 had stage IE, 14 had stage IIE, 2 had stage IIIE, and 5 had stage IVE disease. There was no consistent pattern of treatment identified from our literature review. Primary lymphoma of the uterine cervix is a rare malignancy. Most patients present with stage IE disease. Women with localized disease typically respond to various combinations of surgery, chemotherapy, and radiotherapy. Combination chemotherapy with tailored radiotherapy appears to be the preferred treatment option in women with advanced disease.


Pubertal metrorrhagia.
To determine the clinical characteristics of pubertal metrorrhagia and its treatment, depending on severity; to evaluate the frequency of etiologies and the influence of hemostatic abnormalities; and to describe severe pubertal metrorrhagia. Design, setting and participants. This retrospective study examined all the files (n = 105) of adolescents presenting for pediatric gynecology consultation at a children's hospital between January 1979 and June 1993. The mean age of patients at the first consultation was 13 years. Metrorrhagia began in the year after the first menstrual period in 85% of cases. The causes were functional (83 cases), primary hemostatic disorder (14 cases), hemostatic disorder secondary to renal or hepatic disease (7 cases), or tumor (1 case). The cases were assigned to one of three groups, according to the severity of anemia; group I, mild anemia, hemoglobin Hb > 11 g%, 64 cases; group II, moderate anemia, Hb 8-11 g%, 23 cases; and group III, severe anemia, Hb < 8 g%, 18 cases. Of the 14 patients suffering from primary hemostatic disorders, 7 had been diagnosed before the onset of metrorrhagia; the disorder was revealed by the metrorrhagia in the remaining 7. Only 1 of these patients was severely anemic (known factor X deficiency). Four patients suffering from moderate von Willebrand's disease were discovered after specific tests; they were mildly or moderately anemic. The severe anemias (group III) all occurred during the first three periods. This group had functional disorders in 15 of 18 cases. Treatment continued to be required in 10 of 18 cases followed for more than 3 years. Treatment was progestin for group I and II patients or an estroprogestin, followed by a progestin, for group III. Curettage was never required. The most common cause of pubertal metrorrhagia is a functional disorder (80% of cases). Hemostatic disorders likely to cause severe menstrual hemorrhage were known before the age of menarche; these disorders must be controlled by hormone treatment begun before or at the time of the first menstrual period. Severe forms that arise during the initial three menstrual cycles are functional in most cases. These should be given a course of treatment lasting several years. There is a high risk of recurrence. Treatment is medical and hormonal in all cases.


Interaction of Newly Platinum(II) with Tris(2-carboxyethyl)phosphine Complex with DNA and Model Lipid Membrane.
Structural properties of plasmid DNA and model lipid membrane treated with newly synthesized platinum(II) complex cis-[PtCl2{P(CH2CH2COOH)3}2] (cis-DTCEP for short) were studied and compared with effects of anticancer drug cisplatin, cis-[Pt(NH3)2Cl2] (cis-DDP for short). Time Correlated Single Photon Counting Fluorescence Correlation Spectroscopy (TCSPC-FCS) was employed to study interactions between those platinum complexes and DNA. The TCSPC-FCS results suggest that bonding of cis-DTCEP derivative to DNA leads to plasmid strain realignment towards much more compact structure than in the case of cis-DDP. Application of both differential scanning calorimetry and infrared spectroscopy to platinum complexes/DPPC showed that cis-DTCEP slightly increases the phospholipid's main phase transition temperature resulting in decreased fluidity of the model membrane. The newly investigated compound-similarly to cis-DDP-interacts mainly with the DPPC head group however not only by the means of electrostatic forces: this compound probably enters into hydrophilic region of the lipid bilayer and forms hydrogen bonds with COO groups of glycerol and PO2- group of DPPC.


[ Anti-aging dental medicine and calcium metabolism].
Anti-aging medicine is defined as the medicine which makes maintaining health and youth possible while growing older. Saliva has growth factors and antibacterial agents important for biological homeostasis, and various other substances vital for maintaining general health. The dentistry field also has a deep involvement in dental caries and bone formation (alveolar bone) . This article will discuss recent advances of anti-aging dental medicine including calcium metabolism.


Apoptotic Cell Exclusion and Bias-Free Single-Cell Selection Are Important Quality Control Requirements for Successful Single-Cell Sequencing Applications.
Single-cell sequencing experiments are a new mainstay in biology and have been advancing science especially in the biomedical field. The high pressure to integrate the technology into daily laboratory live requires solid knowledge with respect to potential limitations and precautions to be taken care of before applying it to complex research questions. In the past, we have identified two issues with quality measures neglected by the growing community involving SmartSeq and droplet or micro-well-based scRNASeq methods (1) how to ensure that only single cells are introduced without biasing on light scattering when handling complex cell mixtures and organ preparations or (2) how best to control for (pro-)apoptotic cell contaminations in single-cell sequencing approaches. Sighting of concurrent literature involving single-cell sequencing technologies revealed that these topics are generally neglected or simply approached in silico but not at the bench before generating single-cell data sets. We fear that those important quality aspects are overlooked due to reduced awareness of their importance for guaranteeing the quality of experiments. In this Cytometry rigor issue, we provide experimentally supported guidance on how to circumvent those critical shortcomings in order to promote a better use of the fantastic single-cell sequencing toolbox in biology. © 2019 The Authors. Cytometry Part A published by Wiley Periodicals, Inc. on behalf of International Society for Advancement of Cytometry.


Electrophysiologic testing in the upright position: improved evaluation of patients with rhythm disturbances using a tilt table.
Patients are traditionally evaluated in the supine position in the electrophysiology laboratory, although symptoms due to a cardiac rhythm disturbance are often maximal clinically during standing. The assumption of the upright position results in dependent displacement of blood, followed by prompt vasoconstriction to maintain arterial pressure. This normal response may aggravate tachyarrhythmias by increasing catecholamine levels or may precipitate vasodepressor syncope if the vasoconstrictor response is absent. The use of a tilt table during electrophysiologic testing was evaluated over a 12 month period in 104 patients having a mean age of 60 years (range 37 to 81): 59 with supraventricular tachycardia, 6 with vasovagal syncope and 39 with carotid sinus hypersensitivity. Twenty-three patients (22%) had significant abnormalities when upright that were not present when supine: eight patients with supraventricular tachycardia who had their clinical syndromes of palpitation and syncope reproduced when upright, but only minimal symptoms when supine; two patients with supraventricular tachycardia who had sustained atrioventricular reentry when upright, but only two to eight beats of tachycardia when supine; six patients with syncope and a normal cardiac evaluation before electrophysiologic testing who had their typical spells only after being placed upright during a vasovagal event and seven patients with carotid sinus hypersensitivity who had their clinical syndromes reproduced with carotid sinus massage only when upright, developing hypotension despite maintaining their heart rate with sinus rhythm or pacing (vasodepressor response). In 22% of patients, electrophysiologic testing in the upright position provided clinically important information that was not evident during standard testing in the supine position.


[Action mechanism of sodium polyacrylates against stomach ulcer].
Three sodium polyacrylates (PAS) with different viscosities were examined for antiulcerogenic properties. Rats were fed with sugar containing a PAS for 4 hr and subjected to 12 hr reserpinization or stress by water immersion. Lower incidence of ulceration and larger amount of stomach content after the experiment were found in the PAS administered groups. The higher viscous PAS was more effective in prevention of ulceration and in prolongation of gastric emptying. Intragastric administration of the drugs to pylorus ligated rats reduced forestomach ulceration. However, differences in the antiulcerogenic activity of three drugs were not observed. The effects on the gastric secretion of three PAS (50 mg) were also examined, using pylorus ligated (6 hr) rats. In PAS groups, the free acid in the gastric juice was reduced to some extent. There was, however, no relation between the antiacid effect and viscosity. The drugs inhibited the peptic digestion in vitro, but the difference of viscosity was not related to the antipeptic effect. It is concluded that prolongation of gastric emptying may be a major factor in the antiulcerogenic activity of PAS.


Alcohol use in a continuing care retirement community.
The purpose of this study was to explore alcohol use among older adults living in a continuing care retirement community (CCRC) and to consider differences in overall health, number of chronic illnesses, falls, age, and exercise behavior between those who drink moderately versus those who do not. A one-time face-to-face interview was conducted with a total of 316 residents living in an urban CCRC in the northeast. The participants were 86.6 6 6.3 years of age, and the majority were women (79%), unmarried (75%), White (9%), and middle to upper socioeconomic status (100%). The majority of these individuals (63%) drank moderately, consuming at least one drink daily. No difference was found between men's and women's drinking behaviors (chi 2 = .47, p > .05). Adults who drank moderately were older (F = 8.7, p < .05), more likely to exercise regularly (chi 2 = 27, p < .05), and were more likely to have had a fall (F = 3.7, p < .05). No statistically significant difference was found between the groups related to perceptions of overall health, number of chronic illnesses, number of medications, overall or number of medications that interact with alcohol, or cognitive status. Although not statistically significant, a greater percentage of individuals who drink moderately had fractures (12%) when compared to the percentage of individuals who do not drink at least moderately (7%). Recognizing both benefits and risks to alcohol use in older adults suggests that an individual approach to educating these individuals about their use of alcohol should be conducted.


Wing morphometric variability of the malaria vector Anopheles (Cellia) epiroticus Linton et Harbach (Diptera: Culicidae) for the duration of the rainy season in coastal areas of Samut Songkhram, Thailand.
In Thailand, Anopheles (Cellia) epiroticus Linton et Harbach (Diptera: Culicidae) is the secondary vector of human malaria along coastal regions. While there are some studies of phenotypic variability and population structure of A. epiroticus, more information on morphological variation would enhance epidemiological understanding of medically important mosquito vectors. This research examined morphological variation at three different distances from coastlines of Samut Songkhram Province, Thailand, using landmark-based geometric morphometrics. Wing shape of A. epiroticus was significantly different in the area 0.2 km away from the sea compared to areas 2 and 4 km away from the sea (p < 0.05). Phenotypic variability in wing shape is associated with distance from the sea. Morphological variations in the area closest to the sea were most pronounced, showing a relationship between A. epiroticus and the ecosystem that affects wing geometry. These results provide important information to understand morphological variation of A. epiroticus in coastal areas.


[Progress in the development of a detection test for parenteral non-A, non-B hepatitis--results of enzyme immunoassay for anti-hepatitis C virus].
After more than one decennium of international research work the doubtless identification of the causative agents of the non A-non B-hepatitis (NANBH) has not yet been successful. 1988, however, a viral genome of the parenteral NANBH could be isolated, on which basis an EIA was built up. By means of this anti-HCV-ELISA altogether 413 sera were tested. In 262 sera of 154 women of a NANBH-group with homogeneous source of infection (contaminated anti-D-immunoglobulin) in 74% positive reactions were the result. This and the extensive reproducibility of the test results in identical patients speak for the fact that the recombinant antigen underlying the test really belongs to the parenteral NANBH-group. In the group of the sporadic, however, only in one case a positive reaction was achieved, which supports the thesis of at least two parenteral causative agents of NANBH. The deep-freezing storage of patients' sera lasting up to 8 years did not lead to the failure of the test. The reasons for non-reactive tests were discussed.


Quality of Life Related to Functional Disability in Migraine Patients: A Systematic Review and Network Meta-analysis.
The aim of this study was to conduct a systematic review and network meta-analysis of all randomized trials investigating effect of anti-calcitonin gene-related peptide monoclonal antibodies on disability related to migraine in adult patients. Medline, Embase, and Cochrane Central Register of Controlled Trials searched from inception to July 2020 with an additional review of clinical trial registries. Disability evaluated using change in patient reported Migraine Disability Assessment scores from baseline were considered for the final analysis. The network meta-analysis was conducted in Bayesian framework using OpenBUGS and R, with the random effects model selected to allow for apparent heterogeneity between studies in the treatment comparison effects. Overall 41 studies (7095 migraineurs in 9 randomized trials) were included with treatment course of at least 12 weeks. Subcutaneous injections of fremanezumab 675+225+225 mg QM and 225+225+225 mg QM were more effective in reducing disability in chronic and episodic migraine patients, respectively, with higher median difference in Migraine Disability Assessment score from baseline compared with other treatments including erenumab (70 mg QM; 140 mg QM), galcanezumab (120 mg QM; 240 mg QM), and low doses of fremanezumab (225 mg single dose; 675 mg single dose). For short-term prevention of migraine, fremanezumab demonstrated slightly better improvement in disability compared with other anti-calcitonin gene-related peptide monoclonal antibodies in adult patients with migraine.


High-throughput functional screen identifies YWHAZ as a key regulator of pancreatic cancer metastasis.
Pancreatic cancer is a leading cause of cancer death due to its early metastasis and limited response to the current therapies. Metastasis is a complicated multistep process, which is determined by complex genetic alterations. Despite the identification of many metastasis-related genes, distinguishing the drivers from numerous passengers and establishing the causality in cancer pathophysiology remains challenging. Here, we established a high-throughput and piggyBac transposon-based genetic screening platform, which enables either reduced or increased expression of chromosomal genes near the incorporation site of the gene search vector cassette that contains a doxycycline-regulated promoter. Using this strategy, we identified YWHAZ as a key regulator of pancreatic cancer metastasis. We demonstrated that functional activation of Ywhaz by the gene search vector led to enhanced metastatic capability in mouse pancreatic cancer cells. The metastasis-promoting role of YWHAZ was further validated in human pancreatic cancer cells. Overexpression of YWHAZ resulted in more aggressive metastatic phenotypes in vitro and a shorter survival rate in vivo by modulating epithelial-to-mesenchymal transition. Hence, our study established a high-throughput screening method to investigate the functional relevance of novel genes and validated YWHAZ as a key regulator of pancreatic cancer metastasis.


Aggressive Angiomyxoma in Pregnancy: A Rare Condition, a Common Misdiagnosis.
Introduction. Aggressive angiomyxoma is a rare mesenchymal neoplasm. Although benign in the majority of the cases, these neoplasms usually present a locally infiltrative nature and high rates of recurrence. Due to its rarity, misdiagnosis is a common problem. Case Presentation. We present one case of aggressive angiomyxoma in a 25-year-old pregnant woman. The patient presented with a large vaginal mass that was interpreted as a vaginal cyst. We performed surgical resection of the neoplasm and the correct diagnosis was only achieved after histological examination. With this case, we highlight the importance of considering this diagnosis in patients with genital and perineal masses of unknown origin and the impact of a correct preoperative diagnosis in patient's management and follow-up. Conclusion. Although aggressive angiomyxoma is rare, it should be considered in differential diagnosis of pelviperineal masses in young women. Its positivity to estrogen and progesterone receptors can justify enlargement and recurrence during pregnancy, although few cases are reported. Early recognition demands high index of suspicion for both gynaecologists and pathologists. Wide surgical excision with tumor free margins is the basis of curative treatment. Adjuvant therapy may be necessary for residual or recurrent tumors. Long-term follow-up is recommended.


Sustained ventricular tachycardia in patients with idiopathic dilated cardiomyopathy: electrophysiologic testing and lack of response to antiarrhythmic drug therapy.
Eleven consecutive patients with idiopathic dilated cardiomyopathy and spontaneous, sustained ventricular tachycardia (VT) of uniform morphology underwent programmed ventricular stimulation and serial antiarrhythmic drug testing. The mean ejection fraction was 30 +/- 6.4%. Sustained VT was induced by programmed electrical stimulation in all 11 patients. A mean of 3.7 +/- 2.4 antiarrhythmic drugs were evaluated by programmed stimulation, including at least one experimental agent in eight patients. In nine of 11 patients VT remained inducible on all drug therapy. During a mean follow-up period of 21 +/- 14 months there were four sudden deaths and two patients with recurrences of VT. In all six patients with sudden death or recurrence of VT, the arrhythmia remained inducible on drug therapy. Three patients who died suddenly had a hemodynamically stable, induced tachycardia on antiarrhythmic therapy. Of eight patients treated with amiodarone, only two were successfully treated. We conclude that in patients with sustained VT and idiopathic dilated cardiomyopathy, VT can be induced by programmed electrical stimulation. VT will usually remain inducible on antiarrhythmic therapy, and sudden death can occur despite slowing and improved tolerance of the induced arrhythmia. Amiodarone may have limited efficacy, and more aggressive therapy, such as surgery or implantation of an automatic internal defibrillator, should be considered in this patient population.


Contact angles of pharmaceutical powders.
Contact angles of pharmaceutical powders were determined by measuring the maximum height of a drop of a saturated solution on a presaturated compact of the material. The results for a series of drugs are presented.


Synchronous ganglioneuroma and schwannoma of the vagal inferior ganglion.
Neurogenic neoplasms resulting from autonomic nerves are considerably rare. In this paper, we report a case of a 41-year-old woman with composite tumor of synchronous ganglioneuroma and schwannoma in the vagal inferior ganglion. Ultrasonography and computed tomography showed a well-defined mass, which extruded from the internal and external carotid arteries. Two tumors were closely attached but with an evident boundary. The small tumor was composed of spindle cells and numerous mature ganglion cells, and the large one consisted entirely of differentiated neoplastic Schwann cells. Results showed that these tumors were a schwannoma arising in a ganglioneuroma of the vagal inferior ganglion. Our case is the first to demonstrate the occurrence of schwannoma in benign ganglioneuroma. We also provided clinical and pathological evidence that such transformation can occur spontaneously. .


Modern neuropsychological tests for a diversity of cultural contexts.
The appropriateness of the current neuropsychological tests for the assessment of different populations has been questioned. In this issue several articles have proposed the modernization of neuropsychological testing by incorporating modern technological devices such as computers, mobile phones, or tablets. This is a commentary on the articles contained in the special issue about the inclusion of modern assessment methods that can be properly used around the world and not only in technologically/economically advanced countries. The author of this article reviewed the articles included in the special issue with the goal of commenting on whether the new approaches proposed would have global relevance and applicability. The use of biomedical databases and modern technological devices such as computers, wearables and tablets might not be available in many countries, thus leading to a situation in which modern neuropsychological tests might be available only in some world regions. In addition, because in many countries there are large percentages of population with low education these modern neuropsychological tests might not be appropriate for them. Finally, tests developed with culturally specific stimuli will not be applicable in some cultures. This article provides an overview of several issues that should be considered to make neuropsychological tests both modern and accessible around the world, more specifically the cross-cultural appropriateness and accessibility for low educated individuals and availability in low/middle income regions.


Two cases of Leclercia adecarboxylata septic arthritis in immunocompetent paediatric patients.
Leclercia adecarboxylata is a rare cause of septic arthritis in children, and has intrinsic resistance to common antibiotics. We describe two cases of L. adecarboxylata septic arthritis in children that required re-presentation to hospital with prolonged treatment, and highlight the importance of considering L. adecarboxylata as a potential cause of infection among children with penetrating injuries and associated environmental exposure.


Use of cardiac rehabilitation by Medicare beneficiaries after myocardial infarction or coronary bypass surgery.
Cardiac rehabilitation (CR) is effective in prolonging survival and reducing disability in patients with coronary heart disease. However, national use patterns and predictors of CR use have not been evaluated thoroughly. Using Medicare claims, we analyzed outpatient (phase II) CR use after hospitalizations for acute myocardial infarctions or coronary artery bypass graft surgery in 267,427 fee-for-service beneficiaries aged > or = 65 years who survived for at least 30 days after hospital discharge. We used multivariable analyses to identify predictors of CR use and to quantify geographic variations in its use. We obtained unadjusted, adjusted-smoothed, and standardized rates of CR use by state. Overall, CR was used in 13.9% of patients hospitalized for acute myocardial infarction and 31.0% of patients who underwent coronary artery bypass graft surgery. Older individuals, women, nonwhites, and patients with comorbidities (including congestive heart failure, previous stroke, diabetes mellitus, or cancer) were significantly less likely to receive CR. Coronary artery bypass graft surgery during the index hospitalization, higher median household income, higher level of education, and shorter distance to the nearest CR facility were important predictors of higher CR use. Adjusted CR use varied 9-fold among states, ranging from 6.6% in Idaho to 53.5% in Nebraska. The highest CR use rates were clustered in the north central states of the United States. CR use is relatively low among Medicare beneficiaries despite convincing evidence of its benefits and recommendations for its use by professional organizations. Use is higher after coronary artery bypass graft surgery than with acute myocardial infarctions not treated with revascularization procedures and varies dramatically by state and region of the United States.


Contraction process of an electroactive actuator based on a one microsecond atomistic molecular dynamics simulation.
The contraction process of an electroactive actuator constituted by calix[4]arene units and quaterthiophene segments has been investigated at the microscopic level by using atomistic molecular dynamics simulations in dichloromethane solution using explicit solvent molecules. Results derived from a 1 mus trajectory of the oxidized and deprotonated actuator indicate that the contraction occurs through a non-concerted mechanism in which each actuating units present in the system behave independently. The efficiency of the contraction process can be reduced by the presence of secondary conformational transitions in the calix[4]arene scaffolds. Accordingly, the drastic reduction of the molecular length expected during the contraction process can be limited by such transitions, which involve the rotational isomerism of a phenolate ring. However, such type of conformational transitions does not compromise the actuator power due to its intrinsic capacity to adopt compact molecular arrangements. On the other hand, the rate of the contraction process is influenced by the presence of solvent molecules, which have been found to reduce it by a factor of about 1000.


Ruptured aortic aneurysms: postoperative complications and their aetiology.
A review of 198 ruptured aortic aneurysms has been undertaken, this being 36.3 per cent of all the aneurysms treated during the period 1960-81. The overall mortality rate was 42.9 per cent. The peroperative mortality was 6.6 per cent and the mortality of the patients who survived the operation was 38.9 per cent. Factors which influenced postoperative mortality were the age of the patient, the distance travelled to hospital, the presence of an intraperitoneal bleed, the duration of the operative procedure and the volume of blood transfused, but only the amount of blood transfused had a statistically significant influence on mortality. However, as the highest mortality associated with any of these risk factors was 54.9 per cent, no single factor alone can be considered a contra-indication to operation. As there are no reliable predictive factors, we believe that all cases with clinically ruptured aortic aneurysms should have a laparotomy and resection. The most common postoperative complications were varying degrees of renal and respiratory insufficiency and the occurrence of these was significantly associated with the volume of blood transfused.


Self-administration of medicines.
Self-administration of medicines by patients in hospitals and residential homes can lead to increased comprehension and compliance with treatment after discharge and thus to a reduction in readmission rates. It can also increase the self-esteem of chronically ill patients by allowing them to take responsibility for their own health.


Reducing Maternal Mortality by Strengthening Community Maternal Support Systems: Findings from a Qualitative Baseline Study in Northern Nigeria.
The "three delays model" illustrates how issues around obstetric emergency can lead to maternal deaths. This study applied in-depth interviews of key community gatekeepers in 16 rural communities across two states in northern Nigeria to evaluate the presence and functionality of key community maternal support systems for reducing maternal mortality. Findings show that only one out of the 16 communities had all the key support systems. Five rural communities reported that pregnant women have standing permission to visit health facilities during obstetric emergencies. A quarter of the communities reported the presence of transport for maternal emergencies. One rural community each reported the existence of community savings for obstetric emergencies and the presence of blood donor groups. Establishing and/or strengthening community support systems, ensuring citizens are well-informed about maternal danger signs and preparing for safe pregnancies can enable communities overcome the delays and reduce maternal mortality especially in low resource settings.


Detection of nanosecond-scale, high power THz pulses with a field effect transistor.
We demonstrate detection and resolution of high power, 34 ns free electron laser pulses using a rectifying field effect transistor. The detector remains linear up to an input power of 11 ± 0.5 W at a pulse energy of 20 ± 1 μJ at 240 GHz. We compare its performance to a protected Schottky diode, finding a shorter intrinsic time constant. The damage threshold is estimated to be a few 100 W. The detector is, therefore, well-suited for characterizing high power THz pulses. We further demonstrate that the same detector can be used to detect low power continuous-wave THz signals with a post detection limited noise floor of 3.1 μW/√Hz. Such ultrafast, high power detectors are important tools for high power and high energy THz facilities such as free electron lasers.


Yuzurimine-type alkaloids from Daphniphyllum yunnanense.
Five new yuzurimine-type alkaloids, yunnandaphnines A-E (2-6), together with two known analogues, macrodaphniphyllamine (1) and calycinine A (7), have been isolated from the leaves and twigs of Daphniphyllum yunnanense. The structures of the new alkaloids were elucidated by spectroscopic methods. Yunnandaphnine E (6) is a novel heptacyclic yuzurimine-type alkaloid with an oxazine ring.